Improving morbidity and mortality of breast cancer can be done through efforts in prevention. While there are approved agents for breast cancer prevention, none are available for prevention of estrogen receptor negative disease and there are few options for premenopausal women. New agents are needed;however the studies necessary to identify these chemo preventive agents are large expensive. Evaluation of the effects of potential chemo preventive agents on biomarkers related to cancer risk can provide critical information regarding the true utility of an agent. Positive effects demonstrated on biomarkers can suggest an agent move to the next level of testing with a high probability of success. Lack of affect on biomarkers would suggest not moving to the next step. Thus, the use of intermediate biomarkers in studies of short term interventions are cost effective, aid in the testing of many agents and ensure that only the most promising agents move forward to larger more expensive studies. Biomarkers of breast cancer are known, however not all possess the characteristics necessary for use as an intermediate marker. Biomarkers must be clearly associated with breast cancer risk, and modification of the marker must show a decrease in breast cancer risk. Mammographic breast density has the required characteristics. IGFI and tissue biomarkers (cytologic atypia and Ki67) have some but not all of the required characteristics, thus require more evaluation. Identifying chemoprevention agents for prevention of estrogen receptor negative disease and increasing options for premenopausal women is important. A successful agent must not only prevent disease but have little risk and a tolerable side effect profile. Vitamin D3 is potentially such an agent. Vitamin D has ant carcinogenic properties, affecting apoptosis and differentiation. Several epidemiologic studies link higher vitamin D levels with decrease risk of several types of cancer including breast cancer. Vitamin D3 supplementation is associated with little risk and few side effects. We propose a randomized, placebo controlled trial of one year of vitamin D3 supplementation (2000 IU/day) evaluating the effects on several breast cancer biomarkers (breast density, IGF1, atypia and Ki67). The primary aim will focus on the effects of vitamin D3 on mammographic density. Secondary aims will evaluate the effects on serum biomarkers (IGF1) and tissue biomarkers (cytologic atypia and Ki67). Finding effects of vitamin D3 on breast cancer biomarkers will provide necessary support for a larger chemoprevention trial focusing on breast cancer development. In this manner we hope to identify options for prevention of estrogen receptor negative breast cancer and more tolerable options for premenopausal women. PUBLIC HEALTH RELEVANCE: Identifying safe and acceptable agents for breast cancer prevention of estrogen receptor negative disease and increasing options for premenopausal women is important in order to improve breast cancer morbidity and mortality outcomes. The ant carcinogenic properties of vitamin D are established and several lines of evidence suggest vitamin D may play a protective role against breast cancer. We propose a randomized, placebo controlled study evaluating the effects of 2000 IU/day of vitamin D3 on several breast cancer biomarkers. The findings from this study will provide important information on the potential efficacy, feasibility and safety of supplementing with vitamin D3 and breast cancer risk.